A collaborative project on quantitative studies of nerve regeneration has been initiated. Nerve regeneration can be logically considered in 4 aspects: 1) the peripheral signal; 2) the neuronal growth response; 3) axonal guidance; and 4) termination. Current work is directed at quantitatively evaluating the neuronal growth response in peripheral nerves. To this end we are using neurofilament protein as a neuron-specific marker. We have demonstrated a proximal to distal gradient of phosphorylated NFP in normal sciatic nerves. Nerve crush or transection is followed by depletion of distal NFP and alterations in the normal gradient of NFP proximal to the lesion. This and other markers of neuronal function are being used to investigate the events that occur during the regenerative process and to assess the effects of various experimental regimes.